There exists a vast flora of different biomaterials that can be implanted in the body. These can be categorized according to their in vivo activity as bioinert, resorbable or bioactive materials. Bioinert materials are in a sense seen as foreign objects when they come in contact with living tissue. The body encapsulates the object with thin tissue and hence mechanically fixates the object within the body. Typical bioinert materials are ceramics, such as aluminium oxide and zirconium dioxide and different non-biodegradable polymers. Bioresorbable materials such as tricalcium phosphate, calcium sulfate and biodegradable polymers are used to replace damaged tissue. These are eventually dissolved and replaced by body tissue. Bioactive materials include, for example, hydroxyapatite and some glass and glass-ceramics and are characterized by their ability to initiate a biological response, leading to a chemical and biological binding to the living tissue.
Osseointegration, meaning the integration of an implant for repairing or replacement of hard tissues in a body and the surrounding biological tissue, i.e. bone, is decisive for the success of the implantation procedure. A deficient osseointegration may lead to implant detachment. There are several methods to achieve good osseointegration, for example a) implant design, such as the distance between the threads on dental implant screws (Wennerberg, A., et al., “Design And Surface Characteristics Of 13 Commercially Available Oral Implant Systems,” International Journal of Oral & Maxillofacial Implants, vol. 8, No. 6, pp. 622-623 (1993); Wennerberg A, Albrektsson T, Lausmaa J. Torque and histomorphometric evaluation of c.p. titanium screws blasted with 25- and 75-microns-sized particles of A1203. J Biomed Mater Res 1996; 30: 251-260, and U.S. Pat. No. 4,330,891 to Branemark, et al.), b) tuning of the implant surface topography (Larsson et al, “Implant element” U.S. Pat. No. 6,689,170), c) selecting the right surface chemistry (Ellingsen et al, “Process for treating a metallic surgical implant” U.S. Pat. No. 5,571,188) (R. G. T. Geesink, Clin. Orthop. 261 (1990) 39-58; J. A. Jansen, et al., Mater. Res., 25 (1991) 973-989; T. W. Bauer, et al., Bone Join Surg., 73A (1991) 1439-1452; Rashmir-Raven A M, Richardson D C, Aberman H M, DeYoung D J. The response of cancellous and cortical canine bone to hydroxyapatite-coated and uncoated titanium rods. J Appl Biomater 1995; 6: 237-242.), either bioinert, resorbable or bioactive, and d) a combination of two or all three of a) to c). The driving force for studying osseointegration and its mechanisms is that the patients receiving implant surgery often have to experience a long healing period. Dental titanium implants, for example, typically require a healing time of three to sixth months depending on the patient and the location in the mouth before external loading can be applied.
Hydroxyapatite, HA, Ca10(PO4)6(OH)2, is one of the major mineral components in animal and human bodies, and it gives hardness and strength to bone and teeth. In the body, HA exists as tiny crystals with a needle shaped structure (Lowenstam, H. A., and Weiner, S. On biomineralization, Oxford University Press, New York, 1989.). The needles are roughly 1-2 nm thick, 2-4 nm wide and 20-40 nm in length. HA is, for example, used in percutaneous devices, periodontal treatment, alveolar ridge augmentation, orthopedics, maxillofacial surgery, otolaryngology, and spinal surgery. (Hench (1991) J. Am. Cer. Soc. 74:1487), but is most extensively used for orthopedic and dental implant applications.
Unfortunately, due to low mechanical reliability, especially in a wet environment, HA cannot be used for heavy load-carrying applications by itself (Synthesis and characterization of nano-HA/PA66 composites Mie Huang, Jianqing Feng, Jianxin Wang, Xingdong Zhang, Yubao Li, Yonggang Yan Journal of Materials Science: Materials in Medicine 14 (2003) 655-660). In the body HA is incorporated into another “softer” tissue, thus forming a composite. For example, the human tooth is made up of a mixture of Collagen and HA, which makes it strong against cracking. Today, the most widespread use of synthetic hydroxyapatite is as coatings of titanium implants. This is to enhance the bonding between the implant and the surrounding tissue and to make the binding (osseointegration) as good and rapid as possible. In this application the strength of the titanium together with the biocompatibility of hydroxyapatite is utilized. Even if HA, according to studies, has a bioactive effect, problems with the application of HA have been numerous. Mostly the problems relate to the adhesion of the HA film on the titanium dioxide surface. Poor adhesion results in detachment of the HA film from the implant, which in turn may lead to a total surgical failure. Also, problems with the HA crystallinity have been experienced, leading to dissolution of the film when presented to the living tissue (Wolke J. G. C, Groot K, Jansen J. A, “In vivo dissolution behaviour of various RF magnetron sputtered Ca—P coatings”, J. Biomed. Mater. Res. 39 (4): 524-530 Mar. 15 1998.).
In recent years, research achievements have lead to an increased interest in HA as a bioactive substance and to its use as a coating on implants and other applications. Great efforts have been put into the development of new routes or modifications of old methods to produce more reliable products made of HA. One very promising approach is to make hydroxyapatite in the form of nano-particles. This is because of their ability to sinter at low temperature, their higher specific surface area and that they give stronger end products upon sintering.
Several techniques exist for the making of HA and similar materials in the nano scale. These include controlled chemical precipitation were one utilizes salt solutions of low concentration, vapor deposition techniques (both chemical and physical), condensation from gas phase and different templating techniques, both biological and synthetic. Among synthetic methods, surfactant self-assembly, especially microemulsions where the surfactants forms small water droplets which are used as micro reactors for the purpose of making small particles of HA, have been successfully applied (Susmita Bose et al., Chem. Mater. 2003 (15) 4464-4469; Koumoulidis G C, Katsoulidis A P, Ladavos A K, Pomonis P J, Trapalis C C, Sdoukos A T, Vaimakis T C, Journal of Colloid and Interface Science 259 (2): 254-260 Mar. 15, 2003; Lim G K, Wang J, Ng S C, Gan L M Journal of Materials Chemistry, 9 (7): 1635-1639 July 1999). However, there are problems with the control of both size and morphology as well as low yield of products. Thus, there is a need for a reliable technique for the production of morphologically pure synthetic nano-sized crystalline calcium phosphate, in particular hydroxyapatite.
There are various methods for applying HA films onto implant objects. For example: a) Thermal plasma spray. During the plasma spray process plasma is produced by letting an electric arc pass through a stream of mixed gases. This results in partial melting of a HA feedstock, which in turn is hurled at a relatively high velocity hitting the outer surface of the object to be coated. This treatment gives rise to locally high temperatures, hence affecting the HA crystallinity by giving other polymorphs as well as partial amorphous HA. This amorphous HA has a tendency to dissolve in the body giving poorer osseointegration, Furthermore, the HA-layer is relatively thick (10 μm minimum), which gives problems with regard to adhesion to the implant (Cheang, P.; Khor, K. A. Biomaterials 1996, 17, 537; Groot, K. d.; Geesink, R.; Klein, C.; Serekian, P. L. Biomedical. Mater. Res. 1987, 21, 1375; Story, B.; Burgess, A. Prosthetic implants coated with hydroxylapatite and process for treating prosthetic implants plasma-sprayed with hydroxylapatite; S. Calcitek: USA, 1998; and Zyman, Z.; Weng, J.; Liu, X.; Zhang, X.; Ma, Z. Biomaterials 1993, 14, 225.). b) Sputtering methods, which are relatively high in cost and non-practical due to their low effectiveness (Massaro C, Baker M A, Cosentino F, Ramires P A, Klose S, Milella E, Surface and biological evaluation of hydroxyapatite-based coatings on titanium deposited by different techniques. Journal of Biomedical Materials Research, 58 (6): 651-657 Dec. 5, 2001). C) Electrochemical methods utilizing electrochemistry for growing crystals onto a substrate. This technique has problems with gas formation, which may crack and rupture the coating film. There are several other techniques that are described in the literature, but today only the plasma spray technique is used commercially. Problems utilizing these above described and other not described techniques are plentiful, especially due to that only thick layers can be applied (several μm) leading to problems with adhesion to the substrate and problems with coating objects having complicated shapes. Several of the used or tested techniques also create locally high temperatures, giving amorphous HA instead of the wanted crystalline apatite form. This asks for new coating methods for the depositions of HA onto surfaces. One promising technique is the so-called dip-coating technique where the substrate is dipped into a solution consisting of a particle dispersion. There are several studies made on the use of this technique but problems with the making of a suitable sol has resulted in problems with adhesion to the substrate as well as incoherent films.